ID   TTBK2_HUMAN             Reviewed;        1244 AA.
AC   Q6IQ55; O94932; Q6ZN52; Q8IVV1;
DT   16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 2.
DT   24-JAN-2024, entry version 179.
DE   RecName: Full=Tau-tubulin kinase 2;
DE            EC=2.7.11.1;
GN   Name=TTBK2; Synonyms=KIAA0847;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Cerebellum;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16572171; DOI=10.1038/nature04601;
RA   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA   Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA   FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA   Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA   Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA   DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA   Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA   Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA   Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA   O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA   Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA   Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human chromosome
RT   15.";
RL   Nature 440:671-675(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP   PRO-8.
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 600-1244 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA   Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. XII. The
RT   complete sequences of 100 new cDNA clones from brain which code for large
RT   proteins in vitro.";
RL   DNA Res. 5:355-364(1998).
RN   [5]
RP   INVOLVEMENT IN SCA11.
RX   PubMed=18037885; DOI=10.1038/ng.2007.43;
RA   Houlden H., Johnson J., Gardner-Thorpe C., Lashley T., Hernandez D.,
RA   Worth P., Singleton A.B., Hilton D.A., Holton J., Revesz T., Davis M.B.,
RA   Giunti P., Wood N.W.;
RT   "Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation,
RT   segregate with spinocerebellar ataxia type 11.";
RL   Nat. Genet. 39:1434-1436(2007).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP   LOCATION, AND MUTAGENESIS OF LYS-50; LYS-143; ASP-163; ARG-181 AND ALA-184.
RX   PubMed=21548880; DOI=10.1042/bj20110276;
RA   Bouskila M., Esoof N., Gay L., Fang E.H., Deak M., Begley M.J.,
RA   Cantley L.C., Prescott A., Storey K.G., Alessi D.R.;
RT   "TTBK2 kinase substrate specificity and the impact of spinocerebellar-
RT   ataxia-causing mutations on expression, activity, localization and
RT   development.";
RL   Biochem. J. 437:157-167(2011).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-786, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [8]
RP   INTERACTION WITH CEP164.
RX   PubMed=22863007; DOI=10.1016/j.cell.2012.06.028;
RA   Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H.,
RA   Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J.,
RA   Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H.,
RA   van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H.,
RA   Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A.,
RA   Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S.,
RA   Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S.,
RA   Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C.,
RA   Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G.,
RA   Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A.,
RA   Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R.,
RA   Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J.,
RA   Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A.,
RA   Hildebrandt F.;
RT   "Exome capture reveals ZNF423 and CEP164 mutations, linking renal
RT   ciliopathies to DNA damage response signaling.";
RL   Cell 150:533-548(2012).
RN   [9]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=23141541; DOI=10.1016/j.cell.2012.10.010;
RA   Goetz S.C., Liem K.F. Jr., Anderson K.V.;
RT   "The spinocerebellar ataxia-associated gene tau tubulin kinase 2 controls
RT   the initiation of ciliogenesis.";
RL   Cell 151:847-858(2012).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445 AND SER-1103, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [11]
RP   FUNCTION.
RX   PubMed=30375385; DOI=10.1038/s41467-018-06990-9;
RA   Huang N., Zhang D., Li F., Chai P., Wang S., Teng J., Chen J.;
RT   "M-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97
RT   complex localization at the mother centriole.";
RL   Nat. Commun. 9:4511-4511(2018).
RN   [12]
RP   VARIANTS [LARGE SCALE ANALYSIS] PRO-8; GLN-120; ALA-313; MET-440; PRO-500;
RP   GLY-635; ILE-1062; MET-1084; ALA-1097; ARG-1122 AND THR-1241.
RX   PubMed=17344846; DOI=10.1038/nature05610;
RA   Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA   Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA   Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA   Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA   Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA   Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA   Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA   Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA   Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA   Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA   Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA   Futreal P.A., Stratton M.R.;
RT   "Patterns of somatic mutation in human cancer genomes.";
RL   Nature 446:153-158(2007).
RN   [13]
RP   VARIANTS PRO-8; GLY-842 AND HIS-1110.
RX   PubMed=19533200; DOI=10.1007/s00415-009-5209-0;
RA   Edener U., Kurth I., Meiner A., Hoffmann F., Hubner C.A., Bernard V.,
RA   Gillessen-Kaesbach G., Zuhlke C.;
RT   "Missense exchanges in the TTBK2 gene mutated in SCA11.";
RL   J. Neurol. 256:1856-1859(2009).
RN   [14]
RP   VARIANTS ILE-367 AND GLU-724.
RX   PubMed=26063658; DOI=10.1093/brain/awv155;
RA   Verdura E., Herve D., Scharrer E., del Mar Amador M., Guyant-Marechal L.,
RA   Philippi A., Corlobe A., Bergametti F., Gazal S., Prieto-Morin C.,
RA   Beaufort N., Le Bail B., Viakhireva I., Dichgans M., Chabriat H.,
RA   Haffner C., Tournier-Lasserve E.;
RT   "Heterozygous HTRA1 mutations are associated with autosomal dominant
RT   cerebral small vessel disease.";
RL   Brain 138:2347-2358(2015).
CC   -!- FUNCTION: Serine/threonine kinase that acts as a key regulator of
CC       ciliogenesis: controls the initiation of ciliogenesis by binding to the
CC       distal end of the basal body and promoting the removal of CCP110, which
CC       caps the mother centriole, leading to the recruitment of IFT proteins,
CC       which build the ciliary axoneme. Has some substrate preference for
CC       proteins that are already phosphorylated on a Tyr residue at the +2
CC       position relative to the phosphorylation site. Able to phosphorylate
CC       tau on serines in vitro (PubMed:23141541). Phosphorylates MPHOSPH9
CC       which promotes its ubiquitination and proteasomal degradation, loss of
CC       MPHOSPH9 facilitates the removal of the CP110-CEP97 complex (a negative
CC       regulator of ciliogenesis) from the mother centrioles, promoting the
CC       initiation of ciliogenesis (PubMed:30375385).
CC       {ECO:0000269|PubMed:21548880, ECO:0000269|PubMed:23141541,
CC       ECO:0000269|PubMed:30375385}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC         [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC         Evidence={ECO:0000269|PubMed:21548880};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC         threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC         Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC         EC=2.7.11.1; Evidence={ECO:0000269|PubMed:21548880};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=18 uM for RRKDLHDDEEDEAMSIYpA peptide
CC         {ECO:0000269|PubMed:21548880};
CC         KM=141 uM for RRKDLHDDEEDEAMSIYA peptide
CC         {ECO:0000269|PubMed:21548880};
CC         Vmax=76 umol/min/mg enzyme with RRKDLHDDEEDEAMSIYpA peptide as
CC         substrate {ECO:0000269|PubMed:21548880};
CC         Vmax=66 umol/min/mg enzyme with RRKDLHDDEEDEAMSIYA peptide as
CC         substrate {ECO:0000269|PubMed:21548880};
CC   -!- SUBUNIT: Interacts with CEP164. {ECO:0000269|PubMed:22863007}.
CC   -!- INTERACTION:
CC       Q6IQ55; Q9UPV0: CEP164; NbExp=4; IntAct=EBI-1050303, EBI-3937015;
CC       Q6IQ55; Q53G59: KLHL12; NbExp=6; IntAct=EBI-1050303, EBI-740929;
CC       Q6IQ55-3; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-25930156, EBI-350590;
CC       Q6IQ55-3; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-25930156, EBI-358545;
CC   -!- SUBCELLULAR LOCATION: Cell projection, cilium {ECO:0000250}. Cytoplasm,
CC       cytoskeleton, cilium basal body {ECO:0000250}. Cytoplasm, cytoskeleton,
CC       microtubule organizing center, centrosome, centriole. Cytoplasm,
CC       cytosol. Nucleus. Note=Localizes to the transition zone in primary
CC       cilia in response to cell cycle signals that promote ciliogenesis (By
CC       similarity). May also be present in cytosol and, at lower level in the
CC       nucleus. {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q6IQ55-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q6IQ55-2; Sequence=VSP_018272, VSP_018275;
CC       Name=3;
CC         IsoId=Q6IQ55-3; Sequence=VSP_018273, VSP_018274;
CC   -!- DISEASE: Spinocerebellar ataxia 11 (SCA11) [MIM:604432]:
CC       Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC       group of cerebellar disorders. Patients show progressive incoordination
CC       of gait and often poor coordination of hands, speech and eye movements,
CC       due to degeneration of the cerebellum with variable involvement of the
CC       brainstem and spinal cord. SCA11 is an autosomal dominant cerebellar
CC       ataxia (ADCA). It is a relatively benign, late-onset, slowly
CC       progressive neurologic disorder. {ECO:0000269|PubMed:18037885}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr
CC       protein kinase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AK131372; BAD18523.1; -; mRNA.
DR   EMBL; AC068727; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC090510; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC041876; AAH41876.1; -; mRNA.
DR   EMBL; BC071556; AAH71556.1; -; mRNA.
DR   EMBL; AB020654; BAA74870.1; -; mRNA.
DR   CCDS; CCDS42029.1; -. [Q6IQ55-1]
DR   RefSeq; NP_775771.3; NM_173500.3. [Q6IQ55-1]
DR   PDB; 6U0K; X-ray; 1.74 A; A/B=1-299.
DR   PDB; 6VRF; X-ray; 1.50 A; A/B=1-299.
DR   PDB; 7O3B; X-ray; 2.40 A; G/H/I=1074-1087.
DR   PDB; 7Q8Y; X-ray; 1.60 A; A/B=1-299.
DR   PDB; 7Q8Z; X-ray; 1.57 A; A/B=1-299.
DR   PDB; 7Q90; X-ray; 1.60 A; A/B=1-299.
DR   PDBsum; 6U0K; -.
DR   PDBsum; 6VRF; -.
DR   PDBsum; 7O3B; -.
DR   PDBsum; 7Q8Y; -.
DR   PDBsum; 7Q8Z; -.
DR   PDBsum; 7Q90; -.
DR   AlphaFoldDB; Q6IQ55; -.
DR   SMR; Q6IQ55; -.
DR   BioGRID; 126962; 31.
DR   CORUM; Q6IQ55; -.
DR   IntAct; Q6IQ55; 8.
DR   STRING; 9606.ENSP00000267890; -.
DR   BindingDB; Q6IQ55; -.
DR   ChEMBL; CHEMBL3337327; -.
DR   GlyCosmos; Q6IQ55; 3 sites, 1 glycan.
DR   GlyGen; Q6IQ55; 3 sites, 1 O-linked glycan (3 sites).
DR   iPTMnet; Q6IQ55; -.
DR   PhosphoSitePlus; Q6IQ55; -.
DR   BioMuta; TTBK2; -.
DR   DMDM; 116242833; -.
DR   CPTAC; non-CPTAC-6006; -.
DR   CPTAC; non-CPTAC-6007; -.
DR   EPD; Q6IQ55; -.
DR   jPOST; Q6IQ55; -.
DR   MassIVE; Q6IQ55; -.
DR   MaxQB; Q6IQ55; -.
DR   PaxDb; 9606-ENSP00000267890; -.
DR   PeptideAtlas; Q6IQ55; -.
DR   ProteomicsDB; 66487; -. [Q6IQ55-1]
DR   ProteomicsDB; 66488; -. [Q6IQ55-2]
DR   ProteomicsDB; 66489; -. [Q6IQ55-3]
DR   Pumba; Q6IQ55; -.
DR   Antibodypedia; 6214; 252 antibodies from 30 providers.
DR   DNASU; 146057; -.
DR   Ensembl; ENST00000267890.11; ENSP00000267890.6; ENSG00000128881.18. [Q6IQ55-1]
DR   Ensembl; ENST00000567840.5; ENSP00000455734.1; ENSG00000128881.18. [Q6IQ55-3]
DR   GeneID; 146057; -.
DR   KEGG; hsa:146057; -.
DR   MANE-Select; ENST00000267890.11; ENSP00000267890.6; NM_173500.4; NP_775771.3.
DR   UCSC; uc001zqo.4; human. [Q6IQ55-1]
DR   AGR; HGNC:19141; -.
DR   CTD; 146057; -.
DR   DisGeNET; 146057; -.
DR   GeneCards; TTBK2; -.
DR   GeneReviews; TTBK2; -.
DR   HGNC; HGNC:19141; TTBK2.
DR   HPA; ENSG00000128881; Tissue enhanced (testis).
DR   MalaCards; TTBK2; -.
DR   MIM; 604432; phenotype.
DR   MIM; 611695; gene.
DR   neXtProt; NX_Q6IQ55; -.
DR   OpenTargets; ENSG00000128881; -.
DR   Orphanet; 98767; Spinocerebellar ataxia type 11.
DR   PharmGKB; PA134913925; -.
DR   VEuPathDB; HostDB:ENSG00000128881; -.
DR   eggNOG; KOG1164; Eukaryota.
DR   GeneTree; ENSGT00940000160367; -.
DR   HOGENOM; CLU_003410_0_0_1; -.
DR   InParanoid; Q6IQ55; -.
DR   OMA; EEDWGWG; -.
DR   OrthoDB; 163007at2759; -.
DR   PhylomeDB; Q6IQ55; -.
DR   TreeFam; TF351646; -.
DR   BRENDA; 2.7.11.26; 2681.
DR   PathwayCommons; Q6IQ55; -.
DR   Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR   SABIO-RK; Q6IQ55; -.
DR   SignaLink; Q6IQ55; -.
DR   SIGNOR; Q6IQ55; -.
DR   BioGRID-ORCS; 146057; 11 hits in 1189 CRISPR screens.
DR   ChiTaRS; TTBK2; human.
DR   GeneWiki; TTBK2; -.
DR   GenomeRNAi; 146057; -.
DR   Pharos; Q6IQ55; Tbio.
DR   PRO; PR:Q6IQ55; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; Q6IQ55; Protein.
DR   Bgee; ENSG00000128881; Expressed in lateral nuclear group of thalamus and 193 other cell types or tissues.
DR   ExpressionAtlas; Q6IQ55; baseline and differential.
DR   GO; GO:0005814; C:centriole; IDA:GO_Central.
DR   GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR   GO; GO:0035869; C:ciliary transition zone; IDA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0019894; F:kinesin binding; IPI:ARUK-UCL.
DR   GO; GO:0051010; F:microtubule plus-end binding; TAS:ARUK-UCL.
DR   GO; GO:0004672; F:protein kinase activity; IDA:ARUK-UCL.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR   GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL.
DR   GO; GO:0050321; F:tau-protein kinase activity; TAS:ARUK-UCL.
DR   GO; GO:0021681; P:cerebellar granular layer development; ISS:ARUK-UCL.
DR   GO; GO:0021935; P:cerebellar granule cell precursor tangential migration; ISS:ARUK-UCL.
DR   GO; GO:0021549; P:cerebellum development; ISS:ARUK-UCL.
DR   GO; GO:0060271; P:cilium assembly; IMP:GO_Central.
DR   GO; GO:0000226; P:microtubule cytoskeleton organization; IGI:ARUK-UCL.
DR   GO; GO:1904527; P:negative regulation of microtubule binding; IDA:ARUK-UCL.
DR   GO; GO:0007026; P:negative regulation of microtubule depolymerization; IDA:ARUK-UCL.
DR   GO; GO:1902817; P:negative regulation of protein localization to microtubule; IMP:ARUK-UCL.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR   GO; GO:0030334; P:regulation of cell migration; IGI:ARUK-UCL.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR   CDD; cd14129; STKc_TTBK2; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR017441; Protein_kinase_ATP_BS.
DR   InterPro; IPR047915; TTBK2_STKc.
DR   PANTHER; PTHR11909; CASEIN KINASE-RELATED; 1.
DR   PANTHER; PTHR11909:SF451; TAU-TUBULIN KINASE 2; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   Genevisible; Q6IQ55; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cell projection; Cilium;
KW   Cilium biogenesis/degradation; Cytoplasm; Cytoskeleton; Kinase;
KW   Neurodegeneration; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Serine/threonine-protein kinase;
KW   Spinocerebellar ataxia; Transferase.
FT   CHAIN           1..1244
FT                   /note="Tau-tubulin kinase 2"
FT                   /id="PRO_0000234342"
FT   DOMAIN          21..284
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          674..694
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1052..1088
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1116..1244
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1052..1074
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1116..1133
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1134..1148
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1150..1171
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1184..1212
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1219..1244
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        141
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         27..35
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         50
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         445
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         786
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21406692"
FT   MOD_RES         1103
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         1..72
FT                   /note="MSGGGEQLDILSVGILVKERWKVLRKIGGGGFGEIYDALDMLTRENVALKVE
FT                   SAQQPKQVLKMEVAVLKKLQ -> MES (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_018272"
FT   VAR_SEQ         470..478
FT                   /note="CLEKMQKDT -> WYKIVYFSF (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_018273"
FT   VAR_SEQ         479..1244
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_018274"
FT   VAR_SEQ         1233..1244
FT                   /note="QGKSKPASKLSR -> PREE (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_018275"
FT   VARIANT         8
FT                   /note="L -> P (in dbSNP:rs6493068)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:19533200"
FT                   /id="VAR_041261"
FT   VARIANT         120
FT                   /note="R -> Q (in dbSNP:rs35328266)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041262"
FT   VARIANT         313
FT                   /note="T -> A (in dbSNP:rs56017612)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041263"
FT   VARIANT         367
FT                   /note="K -> I (in dbSNP:rs764753481)"
FT                   /evidence="ECO:0000269|PubMed:26063658"
FT                   /id="VAR_076383"
FT   VARIANT         440
FT                   /note="V -> M (in dbSNP:rs56311523)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041264"
FT   VARIANT         500
FT                   /note="R -> P (in dbSNP:rs56039839)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041265"
FT   VARIANT         635
FT                   /note="D -> G (in a lung small cell carcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041266"
FT   VARIANT         724
FT                   /note="G -> E (in dbSNP:rs201524659)"
FT                   /evidence="ECO:0000269|PubMed:26063658"
FT                   /id="VAR_076384"
FT   VARIANT         842
FT                   /note="E -> G (found in a patient with SCA11; uncertain
FT                   significance; dbSNP:rs202004988)"
FT                   /evidence="ECO:0000269|PubMed:19533200"
FT                   /id="VAR_069052"
FT   VARIANT         1062
FT                   /note="T -> I (in dbSNP:rs55833708)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041267"
FT   VARIANT         1084
FT                   /note="T -> M (in dbSNP:rs34348991)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041268"
FT   VARIANT         1097
FT                   /note="V -> A (in dbSNP:rs55796513)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041269"
FT   VARIANT         1110
FT                   /note="R -> H (found in a patient with SCA11; uncertain
FT                   significance; dbSNP:rs146279300)"
FT                   /evidence="ECO:0000269|PubMed:19533200"
FT                   /id="VAR_069053"
FT   VARIANT         1122
FT                   /note="P -> R (in dbSNP:rs56142516)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041270"
FT   VARIANT         1241
FT                   /note="K -> T (in dbSNP:rs36104367)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_041271"
FT   MUTAGEN         50
FT                   /note="K->E,A: Leads to inactivation/destabilization of the
FT                   protein."
FT                   /evidence="ECO:0000269|PubMed:21548880"
FT   MUTAGEN         143
FT                   /note="K->E,A: Leads to inactivation/destabilization of the
FT                   protein."
FT                   /evidence="ECO:0000269|PubMed:21548880"
FT   MUTAGEN         163
FT                   /note="D->A: Abolishes serine/threonine-protein kinase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:21548880"
FT   MUTAGEN         181
FT                   /note="R->E,A: Impaired serine/threonine-protein kinase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:21548880"
FT   MUTAGEN         184
FT                   /note="A->E,G: Impaired serine/threonine-protein kinase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:21548880"
FT   CONFLICT        309
FT                   /note="T -> I (in Ref. 1; BAD18523)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        456
FT                   /note="T -> A (in Ref. 1; BAD18523)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        557
FT                   /note="K -> N (in Ref. 1; BAD18523)"
FT                   /evidence="ECO:0000305"
FT   TURN            18..20
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          21..28
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           30..32
FT                   /evidence="ECO:0007829|PDB:6U0K"
FT   STRAND          34..40
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   TURN            41..44
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          45..53
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           61..70
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   TURN            71..73
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          80..85
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          87..95
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           101..106
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           109..111
FT                   /evidence="ECO:0007829|PDB:7Q8Z"
FT   HELIX           115..134
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           144..146
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          147..149
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   TURN            153..157
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          159..161
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   STRAND          175..177
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           190..192
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           195..198
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           205..221
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   TURN            225..228
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           232..241
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           244..250
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           255..264
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           273..286
FT                   /evidence="ECO:0007829|PDB:6VRF"
FT   HELIX           296..298
FT                   /evidence="ECO:0007829|PDB:7Q8Z"
SQ   SEQUENCE   1244 AA;  137412 MW;  EAB8FC28370966DE CRC64;
     MSGGGEQLDI LSVGILVKER WKVLRKIGGG GFGEIYDALD MLTRENVALK VESAQQPKQV
     LKMEVAVLKK LQGKDHVCRF IGCGRNDRFN YVVMQLQGRN LADLRRSQSR GTFTISTTLR
     LGRQILESIE SIHSVGFLHR DIKPSNFAMG RFPSTCRKCY MLDFGLARQF TNSCGDVRPP
     RAVAGFRGTV RYASINAHRN REMGRHDDLW SLFYMLVEFV VGQLPWRKIK DKEQVGSIKE
     RYDHRLMLKH LPPEFSIFLD HISSLDYFTK PDYQLLTSVF DNSIKTFGVI ESDPFDWEKT
     GNDGSLTTTT TSTTPQLHTR LTPAAIGIAN ATPIPGDLLR ENTDEVFPDE QLSDGENGIP
     VGVSPDKLPG SLGHPRPQEK DVWEEMDANK NKIKLGICKA ATEEENSHGQ ANGLLNAPSL
     GSPIRVRSEI TQPDRDIPLV RKLRSIHSFE LEKRLTLEPK PDTDKFLETC LEKMQKDTSA
     GKESILPALL HKPCVPAVSR TDHIWHYDEE YLPDASKPAS ANTPEQADGG GSNGFIAVNL
     SSCKQEIDSK EWVIVDKEQD LQDFRTNEAV GHKTTGSPSD EEPEVLQVLE ASPQDEKLQL
     GPWAENDHLK KETSGVVLAL SAEGPPTAAS EQYTDRLELQ PGAASQFIAA TPTSLMEAQA
     EGPLTAITIP RPSVASTQST SGSFHCGQQP EKKDLQPMEP TVELYSPREN FSGLVVTEGE
     PPSGGSRTDL GLQIDHIGHD MLPNIRESNK SQDLGPKELP DHNRLVVREF ENLPGETEEK
     SILLESDNED EKLSRGQHCI EISSLPGDLV IVEKDHSATT EPLDVTKTQT FSVVPNQDKN
     NEIMKLLTVG TSEISSRDID PHVEGQIGQV AEMQKNKISK DDDIMSEDLP GHQGDLSTFL
     HQEGKREKIT PRNGELFHCV SENEHGAPTR KDMVRSSFVT RHSRIPVLAQ EIDSTLESSS
     PVSAKEKLLQ KKAYQPDLVK LLVEKRQFKS FLGDLSSASD KLLEEKLATV PAPFCEEEVL
     TPFSRLTVDS HLSRSAEDSF LSPIISQSRK SKIPRPVSWV NTDQVNSSTS SQFFPRPPPG
     KPPTRPGVEA RLRRYKVLGS SNSDSDLFSR LAQILQNGSQ KPRSTTQCKS PGSPHNPKTP
     PKSPVVPRRS PSASPRSSSL PRTSSSSPSR AGRPHHDQRS SSPHLGRSKS PPSHSGSSSS
     RRSCQQEHCK PSKNGLKGSG SLHHHSASTK TPQGKSKPAS KLSR
//